Yehui Sun, a graduate student in the Siegwart Lab, has been honored with the 2025 Ida M. Green Award for research developing lipid nanoparticles that deliver molecular gene editing machinery to lung cells to treat the genetic lung disease cystic fibrosis (CF).

Ms. Sun’s research focuses on expanding the application of a technology called Selective Organ Targeting, or SORT, that was developed by Daniel Siegwart, Ph.D., at UT Southwestern. First reported in 2020, SORT delivers the RNA-based gene editing tool CRISPR and related technologies to specific cell types. SORT represents a paradigm shift in lipid nanoparticle drug carriers, which typically migrate to the liver based on their strong chemical similarity to low-density lipoprotein (LDL), the “bad” cholesterol particle produced and recycled by this organ. By adjusting the lipid nanoparticles’ ingredients, the Siegwart Lab redirected delivery to other organs in the body, including the lungs and spleen.

Daniel Siegwart, Ph.D., Professor of Biomedical Engineering and Biochemistry, (left) mentors Ms. Sun in his lab, where the two work to expand uses of a technology he developed called Selective Organ Targeting.

In research recognized by the Green Award, Ms. Sun adapted SORT to treat CF in a mouse model of this disease. Although the drug Trikafta can treat most patients with CF, about 10% of patients carry a mutation that renders this gold-standard therapy ineffective. Gene editing holds the most promise in treating these patients, Ms. Sun explained. However, because the lung lining renews itself every few months, editing the disease-causing genes in stem cells is essential to providing a long-lasting therapy – a feat that had yet to be achieved.

After adjusting the composition of the lipid nanoparticles and using them to package base editing machinery – an offshoot of CRISPR – Ms. Sun and her colleagues showed that this intervention successfully corrected genes in about 70% of lung stem cells. After 22 months, these edits persisted, suggesting that a single dose may be enough to treat CF long term. The findings were published in Science.

“I have had the privilege of witnessing her remarkable academic achievement in advancing RNA therapeutics and her outstanding contributions to our graduate school community. She has a bright future ahead,” said Dr. Siegwart, her mentor and Professor of Biomedical Engineering, Biochemistry, and in the Harold C. Simmons Comprehensive Cancer Center.

Ms. Sun, a fifth-year graduate student who expects to earn her Ph.D. this year, said her doctoral work is a culmination of her academic interests. Encouraged by a high school chemistry teacher in Shanghai, China, she attended Northeastern University in Boston for undergraduate and master’s degrees in chemistry. In addition to working there in an academic lab focused on improving the delivery of oligonucleotide therapeutics, she completed internships with Moderna and Takeda Pharmaceutical Co., also focused on drug delivery methods.

Ms. Sun conducts an experiment identifying the lead lipid nanoparticle formulation using reporter gene mRNA.

After a year working as a research associate at the Massachusetts Institute of Technology under Robert Langer, Sc.D. – a scientist focused on drug delivery and Dr. Siegwart’s own postdoctoral adviser – Ms. Sun began her doctoral studies at UTSW. She was drawn to the Siegwart Lab not only for its focus on targeted gene editing, she said, but also for its people.

“Dan has always been very supportive of my research and my career journey. His lab is also unique,” she said. “Not only are about half the members students, but about half are female. We support each other and share ideas, and it’s a great environment to be in.”

A key element of the Green Award is its recognition of community leadership. As Director of Engagement and a board adviser for UTSW’s Biotechnology Club, Ms. Sun launched over 10 high-impact biotech seminars reaching more than 500 people, providing networking and skill-building opportunities for fellow students and trainees. She also helped facilitate the “She-E-O Series” – seminars featuring women founders, executives, and leaders speaking about their journeys and the challenges they have overcome – and patient panels, in which patients and their families discuss how research being performed in UTSW labs has the potential to change their lives.

A month after her Science paper published, Ms. Sun received an email from the family of a cystic fibrosis patient who is part of the minority group unable to be treated with Trikafta, thanking her for the promising research.

“That was the moment I felt like the work we’re doing has something more than its scientific value,” she said. “I believe it will actually make a real impact on patient care.”

The Ida M. Green Award honors the late Mrs. Green. She and her husband, the late Cecil H. Green, were generous supporters of UT Southwestern. The award is given annually to a female student in UT Southwestern’s Graduate School of Biomedical Sciences who has demonstrated scholastic excellence, outstanding support of fellow students, and commitment to the UTSW community. The Green Award is presented by Southwestern Medical Foundation and includes a $2,000 prize.

“Ms. Sun exemplifies the innovation and leadership the Ida M. Green Award was created to honor,” said Michael McMahan, President and CEO of Southwestern Medical Foundation. “Her groundbreaking work in gene therapy for cystic fibrosis offers hope for patients and reflects her commitment to bringing scientists together in ways that strengthen discovery and care.”